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6 Fat body

REV I SED AND UPDATED BY DEBORAH K. HOSHIZAK I

INTRODUCTION

The fat body is a dynamic organ that plays a central role in the metabolic

function of the insect. It is of mesodermal origin and is located in the hemocoel,

with all the cells in close contact with the insect hemolymph, facilitating exchange

of metabolites. The fat body has sometimes been described as equivalent to a

combination of the adipose tissue (storage function) and liver (major metabolic

functions) of vertebrates, but this comparison does not do full justice to the fat body,

which is also a major endocrine organ, and central to systemic immunity of insects.

In addition, the fat body monitors and responds to the physiological needs of the

insect during different developmental stages and under different environmental

conditions, thereby coordinating insect growth with metamorphosis and

reproduction.

This chapter is divided into three parts. Section 6.1 describes the structure

and development of the fat body. It is followed by Section 6.2 on the storage and

utilization of energy and nutrients, and, finally, Section 6.3 on the role of the fat body

as an endocrine organ and nutrient sensor. The effectors of the humoral immune

system derived from the fat body are considered in Chapter 5 (Section 5.3.4).

The Insects: Structure and Function (5th edition), ed. S. J. Simpson and A. E. Douglas. Published by Cambridge University Press.© Cambridge University Press 2013.


6.1 Fat body structure and development

The fat body consists of thin sheets or ribbons,

usually only one or two cells thick, or of small

nodules suspended in the hemocoel by connective

tissue and tracheae. All of its cells are consequently

in immediate contact with the hemolymph,

facilitating the exchange of metabolites. There is

generally a peripheral, or parietal, fat body layer

immediately beneath the body wall, and often a

perivisceral layer surrounding the alimentary canal

can also be distinguished (Fig. 6.1). The fat body is

most conspicuous in the abdomen, but components

extend into the thorax and head. The structure of

the fat body is generally uniform among individuals

of individual species, but there is considerable

variation among species, especially across different

insect orders.

In hemimetabolous insects, the larval fat body

persists in the adult without major changes. In

holometabolous insects, the fat body undergoes a

striking transformation during metamorphosis in

which the tissue dissociates into individual cells. In

the majority of the holometabolous insects, the adult

fat cells are rebuilt from the larval fat cells, but in

Hymenoptera and the higher Diptera, the adult fat

cells develop de novo (Section 6.2.5).

6.1.1 Trophocytes

The principal cells of the fat body are trophocytes

(adipocytes), which store energy. In many insect orders

these are the only cells present within the fat body.

The trophocytes are held together by desmosomes to

form sheets of tissues. The cytoplasm of adjacent

trophocytes is connected through gap junctions, and the

whole tissue is clothed in a basal lamina that is attached

to the cells by hemidesmosomes (Fig. 6.2). The fat body

of some insects additionally contain one or more of

urate cells, mycetocytes and oenocytes. In a number

of Lepidoptera and Diptera, the larval fat body is

regionally differentiated to perform different functions.

For example, in the larva of Helicoverpa (Lepidoptera)

during the period just before pupation, protein synthesis

occurs only in the peripheral fat body, while the storage

of arylphorin and a very high-density lipoprotein,

colored blue by non-covalently bound biliverdin, is

restricted to the cells of the perivisceral fat body. In

Drosophila melanogaster (Diptera), different pigments

for the adult eye are synthesized and sequestered in

different parts of the larval fat body, and in the larva of

Chironomus (Diptera), hemoglobin synthesis appears to

occur in the peripheral fat body, while storage might

occur in the perivisceral fat body cells.

The form of the trophocyte varies according to

developmental stage and nutritional status of the

insect. In a larva soon after ecdysis, the trophocytes

are generally small, with relatively little cytoplasm

and little development of organelles. There are few

mitochondria following the cell division preceding

ecdysis (Fig. 6.3a,d), but, in a well-fed insect, there

follows a preparative phase during which the

trophocytes develop their capacity for synthesis. In the

final larval stage of the moth Calpodes (Lepidoptera)

the preparative period lasts about 66 hours. During this

period there is extensive replication of DNA, but no

nuclear division (Fig. 6.3a, b). Most of the cells become

octaploid, although some cells exhibiting 16- and

32-ploidy also occur. A similar development occurs in

Rhodnius (Hemiptera), while in Calliphora (Diptera),

and probably in other Diptera, polyteny occurs (the

heart

muscle

silk gland

midgutperivisceral fat body

peripheral fat body

nerve cord

Figure 6.1 Distribution of fat body in a caterpillar in

transverse section of the abdomen.

6.1 Fat body structure and development 133


gap junction

mitochondria

basal lamina

lipiddroplet

plasma membranereticular system

desmosome

roughendoplasmic

reticulum

plasma membranereticular system

basallamina

0.1µm

0.1µm

(c)

(a)

(d)

(b) 1.0 µm

Figure 6.2 Structure of a

mature trophocyte. (a)

Diagram of a trophocyte.

(b) Transmission electron

micrograph of the plasma

membrane reticular

system of a trophocyte

from the larva of Calpodes.

(c) Gap junction between

two trophocytes in the

fat body of Calpodes.

(d) Desmosome joining

two trophocytes in the fat

body of Calpodes (b, c and

d after Dean et al., 1985).

134 Fat body


chromosomes divide, but do not separate). At the same

time RNA synthesis occurs (Fig. 6.3c), ribosomes

increase in number, rough endoplasmic reticulum

proliferates and the numbers of mitochondria increase

by division (Fig. 6.3d). The trophocytes now have the

apparatus necessary to begin synthesis. During the

preparative period, the cell membrane invaginates in a

series of folds which interconnect to form the plasma

membrane reticular system (Fig. 6.2). In Calpodes the

membranes in this systemare separated fromeach other

by 100–150 nm. The reticular system occupies the

peripheral 1–1.5 mm of the cells and it presents an

exceptionally large surface area to the hemolymph.

However, this surface is negatively charged and the

effect of this is to limit the access of some large charged

molecules to the interior of the reticulum. It is possible

that the reticulum is concerned with the docking and

unloading of lipophorins. When the larva is

approaching the molt to pupa, the components of the

cell that have been involved inprotein synthesis regress.

Immediately after eclosion, the trophocytes of adult

insects commonly contain extensive lipid droplets,

accumulations of glycogen and protein granules. The

trophocytes in males do not show further

development and they probably play no further major

role in protein synthesis. In females, however, changes

occur which are comparable with those occurring in

larval stages. This reflects the need, in many species,

for the synthesis of vitellogenins.

6.1.2 Urate cells

Urate cells, or urocytes, are present in Collembola

(springtails), Thysanura (silverfish), Blattodea

freq

uenc

yecdysis ecdysis

larva 4 larva 5 pupa

days

repl

icat

ion

synt

hesi

s

num

ber

2 4 6 8 10 12

200

400

600

800

prepphase

syntheticphase

NO DATA

(b) DNA replication

(d) number of mitochondria

(a) frequency of mitoses

(c) RNA synthesis

Figure 6.3 Changes occurring in the cells of the fat body of

the caterpillar of Calpodes during a molt/intermolt cycle

(prep phase is preparatory phase) (mainly after Locke,

1970). (a) The frequency of mitoses. Mitosis is limited to the

period immediately before ecdysis. (b) DNA replication. The

broken line is the presumed phase of replication associated

with mitosis. The solid line shows measured replication

which was not associated with cell division. (c) RNA

synthesis in the cytoplasm. This occurs primarily in the

preparatory phase. (d) Numbers of mitochondria in one cell

(from Dean et al, 1985).

6.1 Fat body structure and development 135


(cockroaches) and larval Apocrita (Hymenoptera)

(bees and wasps). These cells characteristically

contain large crystalloid spherules of uric acid. Uric

acid also accumulates as small granules in all fat

body cells of larval and pupal Lepidoptera and in

larval mosquitoes. For Collembola, which lack

Malpighian tubules, and for Apocrita larvae, which

are confined within their nest cells, the accumulation

of uric acid might provide a mechanism to sequester

nitrogenous waste products. This might also be true

in Lepidoptera, where uric acid accumulates during

the larval wandering phase and continues to

accumulate during the first part of the pupal period,

but then is transferred to the rectum to be excreted in

the meconium. In the cockroaches, however, uric acid

provides a store of nitrogen that can be recycled

(Section 18.5.2).

6.1.3 Hemoglobin cells

Respiratory proteins such as hemoglobin have been

thought to be unnecessary in insects because the

tracheal system efficiently supplies oxygen to the

respiring tissues. However, genes for hemoglobin

have been detected in every insect genome sequenced

to date, and intracellular hemoglobins have been

identified in the fat body and tracheal system of

various insects. Specialized hemoglobin cells have

been described for botfly larvae (Oestridae, Diptera)

and backswimmers (Notonectidae, Hemiptera) that

occur in potentially hypoxic habitats (Section 17.4).

Hemoglobin cells are large, measuring 20–80 mm in

Anisops (Notonectidae) and up to 400 mm in diameter

in Gasterophilus (Oestridae, Diptera). The hemoglobin

cells are closely associated with tracheae.

6.1.4 Other cells

Mycetocytes are cells containing microorganisms

that are localized in the fat body of cockroaches

and some Hemiptera (Section 4.4). Oenocytes,

derived from the epidermis, are also associated with

the fat body in some groups, such as Hemiptera

(Section 16.1.2).

6.1.5 Development and maturationof the fat body

The origin of the insect fat body has primarily been

studied in Drosophila melanogaster, where technical

advances in cell biology tools (e.g., green fluorescent

protein tags), the availability of the complete genome

sequence and extensive genetic tools have allowed

cell lineage tracing studies. These studies reveal the

mesodermal origin of the fat cells and the formation

of the fat body by the coalescence of individual

embryonic fat-cell clusters.

The fat body of the D. melanogaster larva is

derived from cell clusters that arise from the

embryonic mesoderm. The organization of the cell

clusters depends upon patterning genes, including

the pair-rule genes that subdivide the mesoderm

and establish segment identity. These, in turn,

serve to establish the expression of a transcription

factor, Serpent (a member of the family of GATA

transcription factors characterized by their ability

to bind to the DNA sequence GATA), which

specifies the fat-cell fate. The progenitor fat

cells proliferate and coalesce to form the three

morphological domains of the fat body: the dorsal

fat-cell projections, which extend in the anterior

direction from the posterior–dorsal region of the

lateral fat body; the lateral fat body, which spans

the lateral region of the embryo; and the ventral

commissure, which extends from the anterior fat

body and spans the ventral midline. The embryonic

fat body persists into the larva and the domain

structure identified in the embryo is maintained in

the larva. This organization is likely to characterize

all Diptera, although a detailed comparative study

has not been carried out.

Metamorphosis in holometabolic insects is

characterized by a complete change in body plan

controlled in part by pulses of the steroid hormone

20-hydroxyecdysone (20E) (Section 15.3) that induce

programmed cell death of most larval tissues, except

for the fat body. For example, during metamorphosis

of the skipper butterfly, Calpodes ethlius

136 Fat body


(Lepidoptera), the individual fat cells reorganize into

nodular clumps surrounding the tracheoles, and then

undergo classical autophagy, where the intra-cellular

remodeling takes place. The mitochondria,

microbodies and rough endoplasmic reticulum

become sequestered in organelle-specific autophagic

vacuoles and are destroyed by hydrolytic enzymes,

but the cell retains its integrity. After intra-cellular

remodeling, a new round of organelle biogenesis

takes place to generate the adult fat.

The larval fat body of D. melanogaster and

probably other Diptera is also refractive to

20E-triggered programmed cell death. In the pupal

D. melanogaster, the larval fat body persist but the

tissue dissociates into individual cells. The resultant

cells become dispersed throughout the pupa and are

carried forward into the adult. At 3–4 days

post-eclosion, the larval fat cells are replaced by

adult fat cells that arise de novo from cells of the

dorsal thoracic and eye-antennal imaginal discs

and larval histoblasts. The mechanism linking

ecdysteroid signaling and fat body remodeling is

not fully understood, but appears to be an intrinsic

property of the fat body tissue and not determined

by signaling or interactions with other organs.

6.2 Storage and utilization of energyand nutrients

The fat body functions in many aspects of energy

storage and synthesis of proteins, lipids and

carbohydrates. Lipids are stored as triglycerides, and

carbohydrates are stored as glycogen, i.e., polymers

of glucose. The mobilization of these macronutrients

is controlled by the adipokinetic hormone (AKH)

family of peptides and the family of insulin-like

peptides (ILPs). AKH is produced by the corpus

cardiaca, whereas ILPs are produced in the median

neurosecretory cells of the brain, the corpus allatum,

the corpus cardiaca and peripheral tissues including

the fat body. The ratio of triglyceride to glycogen

in the fat body varies among insect species, and with

lifecycle stage and environmental stress, with

triglycerides being the primary component.

In holometabolous insects, animals do not feed

during metamorphosis, and in some cases the adult

itself may not feed, e.g., the silkworm moth, Bombyx

mori (Lepidoptera). Therefore, adequate nutrients

must be stored in the fat body during the larval

stage to support development of the adult tissues

and to support the adult until feeding. This life

history trait places the larval fat body in a unique

position where energy storage and utilization is

monitored for both immediate use and later use by

the pupa and adult. Thus, the cells of the larval

fat body serve as a physical link to carry larval

nutrients into the adult. These larval fat cells provide

nutrient reserves important for ovary maturation in

the adult and can be mobilized in the event of adult

starvation stress.

6.2.1 Lipids

The fat body is the principal storage site of lipids in

insects. Most of the lipid is present as triacylglycerol

(triglyceride), which commonly constitutes more

than half of the dry weight of the fat body. The

amount stored varies with the stage of development

and state of feeding of the insect. Lipid stores

normally increase during periods of active feeding

and decline when feeding stops (Fig. 6.4) or when

large quantities of lipid are used during oogenesis or

prolonged flight.

The lipids are stored in lipid droplets within the

trophocytes. Many triglycerides are synthesized from

diacylglycerides derived from fatty acids or proteins.

Fatty acids can be rapidly taken up by the fat body

and converted to triglycerides. Dietary carbohydrates

can also be converted to triglycerides in the fat body.

Lipids are important because they are a more efficient

form of energy storage than carbohydrates, for two

reasons. First, lipids contain approximately twice the

amount of energy per gram than carbohydrates, and

second, glycogen contains substantial water of

hydration, while lipid droplets contain little or no

6.2 Storage and utilization of energy and nutrients 137


water. Although water of hydration may be released

when glycogen is metabolized under dry conditions,

its additional weight is disadvantageous for activities

such as flight.

Factors stimulating lipid synthesis in insects

have not been defined, but the target of rapamycin

(TOR) signaling pathway has been implicated in

the regulation of nutrient uptake, storage and

metabolism. There is considerable evidence that

juvenile hormone inhibits lipid synthesis, but its

mechanism of action is not known.

6.2.2 Proteins and amino acids

The fat body is the principal site of synthesis of

hemolymph proteins, described in Section 5.3.4.

In the larva of Calpodes, the fat body synthesizes

14 out of 26 hemolymph polypeptides, amounting

to about 90% of the total hemolymph protein.

In adult females the fat body produces vitellogenin,

the protein that will form most of the yolk protein

in the eggs.

Diapause proteins are also produced by the fat

body. For example, adult Colorado potato beetles,

Leptinotarsa (Coleoptera), enter diapause under

short-day conditions. The adult beetles synthesize

vitellogenins and diapause proteins under all

conditions. If newly eclosed beetles experience long

days, vitellogenins are synthesized at a high rate, and

production of diapause proteins is low. In short days

(less than ten hours of light), however, relatively little

vitellogenin, but more of the diapause proteins are

produced.

As the insect prepares to pupate, protein synthesis

in the fat body stops. Proteins, originally

synthesized in and secreted by the fat body are now

removed from the hemolymph and stored as

granules in the fat body (Fig. 6.5). Some protein

uptake does occur during the phase of protein

synthesis, but the uptake is non-selective and

proteins are hydrolyzed within the cells. Protein

breakdown ceases at the end of the period of

synthesis, and the uptake of proteins is selective;

different proteins are taken up to different extents.

In both Helicoverpa (Lepidoptera) and Sarcophaga

(Diptera), this selective uptake of specific proteins is

dependent on the appearance of specific receptor

proteins in the plasma membranes of the fat body.

A precursor of the receptor protein is already

present in the larval fat body of Sarcophaga, and its

conversion to the receptor for the uptake of storage

protein is activated by molting hormone in the

hemolymph before pupation. In Helicoverpa, the

receptor protein for the blue-colored protein is

formed de novo at the time of pupation. This

receptor is only present in the membranes of cells

in the perivisceral fat body, not in the peripheral

fat body.

060 100 12080

time (hours)

2000

4000

area

(µm

2 )

6000

8000

ecdysis

cytoplasm

protein granules

glycogen

lipid droplets

nucleus

larva 3 pupaecdysis

Figure 6.4 Changes in the amounts of the

major components of a trophocyte

during the final larval and pupal stages

of Drosophila. The major increases occur

during the period of feeding. Amounts

are expressed as the areas occupied by

the components in cross-sections of the

tissue. Data from Butterworth et al.

(1965).

138 Fat body


The factors regulating protein synthesis and

storage are not known with certainty, although both

juvenile hormone and ecdysteroids are involved. For

example, the synthesis of arylphorin in the larval

silkworm Bombyx is suppressed by juvenile hormone.

Synthesis is initiated when juvenile hormone is no

longer detectable in the hemolymph of the final

larval stadium hemolymph. In adult insects of most

orders, synthesis of vitellogenin is stimulated by

juvenile hormone, although in Diptera this function

is performed by ecdysteroids (see Fig. 13.10).

The fat body plays an important role in amino acid

metabolism, principally because it is a major site of

transamination between amino acids (Section 4.1.2).

It also contributes to the regulation of the amino acid

tyrosine content of the hemolymph. Tyrosine functions

in cuticle sclerotization and accumulates in the

hemolymph just before a molt (Section 16.6.2). In the

inter-molt period of some insects, tyrosine is taken up

from the hemolymph and stored in large vacuoles in

the trophocytes. This has been most comprehensively

studied in the fourth larval stadium of Calpodes, where

the uptake of tyrosine begins about one day after

ecdysis. Shortly before the next ecdysis, tyrosine is

released into the hemolymph (Fig. 6.6). Additionally or

alternatively, some insects store conjugated tyrosine

(e.g., as glucoside) in the hemolymph (see Fig. 16.17).

6.2.3 Carbohydrates

Carbohydrate is stored in the fat body as glycogen

and circulates in the hemolymph in the form of

trehalose. The amount of stored glycogen in the fat

body is determined in part by the levels of trehalose

in the hemolymph. Both glycogen and trehalose are

synthesized in the fat body from UDP-glucose, which

is derived from dietary carbohydrates or amino acids.

As the level of trehalose rises, its synthesis in the fat

body is inhibited and UDP-glucose is diverted to

glycogen synthesis. Glycogen also serves as a source

of cryoprotectants in over-wintering insects.

ecdysis ecdysis ecdysis

15

10

5

00 5 10

age (days)15 20

fat body

hemolymph

larva 5 pupa adult

25

Figure 6.5 Amounts of blue-colored very-high-density

lipoprotein present in the fat body and hemolymph in

various stages of development of Helicoverpa (after

Haunerland et al. 1990).

ecdysis

larva 4molt

ecdysislarva 5

60 vacuoles (% of fat body)

fat body tyrosine(µmoles g–1)

hemolymph tyrosine(µmoles 10ml–1)

40

20

0654

time (days)

32100

20

40

60 Figure 6.6 Changes in the tyrosine

content of the fat body and hemolymph

of Calpodes larva. Tyrosine in the fat

body is sequestered in vacuoles and the

proportion of the fat body occupied by

vacuoles is paralleled by changes in the

tyrosine content. At ecdysis the vacuoles

disappear as they release tyrosine into

the hemolymph (after McDermid and

Locke, 1983).



In caterpillars, and probably in other insects,

glycogen accumulates in the fat body during periods

of active feeding. This store becomes depleted during

sustained activity or over a molt, when the insect is

not feeding, or if it is starved. For example, the

glycogen content of the fat body of a well-fed

migratory locust, Locusta (Orthoptera), is about

20 mg g�1 fresh weight. Of this, 75% is consumed

after two hours of flight. In Manduca (Lepidoptera)

larvae, the hemolymph concentration of trehalose is

maintained by conversion of glycogen to trehalose in

the fat body (Fig. 6.7).

6.2.4 Mobilization of energy stores

Starvation and high activity levels stimulate the

release of energy reserves from the fat body. During

starvation, stored triglycerides can be metabolized

through the hormonal stimulation of lipases.

Mobilized lipids are ultimately transported to various

target tissues, where the energy is released by

b-oxidation of fatty acids, thereby allowing for

continued growth and survival. The fat body is the

principal tissue involved in starvation-induced

autophagy, a process which degrades and recycles

macromolecules and organelles. A unique feature of

the larval fat cells of dipterans is that the larval fat

cells which are brought forward into the adult serve as

an energy reservoir that can be used during starvation

stress and are critical to the maturation of the ovaries.

The AKH family of peptides are critical for

regulating the supply of energy to tissues, such as the

flight muscles to maintain long-distance flight.

Depending on the insect species, lipids,

carbohydrates, proline or a combination of these

substrates are released from the fat body during times

of metabolic need. Peptides that primarily mobilize

lipids are referred to as adipokinetic hormone, while

peptides whose predominant role is to mobilize

carbohydrates are known as hypertrehalosemic

hormones (HrTH). The HrTH mobilize carbohydrates

by mobilizing trehalose. The adipokinetic and

hypertrehalosemic functions of AKH peptides are

similar to the metabolic responses induced by the

vertebrate hormone, glucagon. In some insects AKH

peptides stimulate the synthesis of proline, while in

the tsetse fly (Glossina morsitans) and Coleoptera,

proline is released into the hemolymph to provide

fuel for the flight muscles.

10

12

14

16

18

starved

fed

0

200

400

600fed

starved

conc

entr

atio

n (µ

gm

l–1)

conc

entr

atio

n (m

gm

l–1)

(c) active phosphorylase

(b) glucose

(a) total sugar

10

20

30

40

50starved

fedamou

nt (

%)

0 2 4 6 8 10

time (h)

0

Figure 6.7 The effects of starvation on carbohydrate

metabolism in a well-fed final-stage larva ofManduca (after

Gies et al., 1988). (a) Concentration of total sugars, mainly

trehalose, in the hemolymph. (b) Concentration of glucose

in the hemolymph. (c) Percentage of active glycogen

phosphorylase in the fat body.

140 Fat body


In addition to AKH signaling, the insulin signaling

pathway regulates nutrient uptake, storage and

metabolism. In insects, the insulin and insulin-like

growth factor (IGF) signaling pathways function as a

single pathway, the insulin/IGF pathway (IIS). In the

IIS pathway both IGFs and ILPs bind to a single

receptor, the insulin receptor (InR) (Fig. 6.8). In

D. melanogaster ILP accessibility is regulated by

IGF-binding proteins (IGF-BPs), which sequester the

ILPs and protect them from degradation. Release of ILP

from the complex allows binding to InR and activation

of the IIS pathway. The IIS pathway promotes nutrient

storage by inserting glucose transporters into the cell

membrane to increase accumulation of sugars,

phosphorylation of glycogen synthase to increase

glycogen storage and by inactivation of the

translational repressor FOXO (Fig. 6.8).

6.2.5 Larval energy stores in adults

In holometabolous insects distinct developmental

stages are tightly linked to feeding (larva and most

adults) and non-feeding periods (pupae and some

adults). In D. melanogaster, and probably other

Diptera, the larval fat cells generated by the

remodeling of the fat body during metamorphosis

(Section 6.1.5) are present in the newly eclosed adult.

Within 24 hours, 85% of the larval fat cells are

destroyed within the adult by the process of

programmed cell death. Presumably the role of the

fat cells is to provide an energy reserve to support the

adult prior to feeding. In D. melanogaster, for

example, the adults do not feed for the first eight

hours.

For Lepidoptera, stable carbon isotope studies

indicate that all the essential amino acids in the eggs

deposited by adult females are derived from larval

feeding, whereas non-essential amino acids are

produced from the adult diet. Presumably, some

of the essential amino acids are derived from

storage proteins, but this has not been demonstrated

directly.

Direct demonstration of a role for larval fat

cells as a nutrient reserve in the adult comes

from starvation experiments. Immature adult

D. melanogaster (within ten minutes of emergence)

P13K

sugar accumulationglycogen storage FOXO

growthnutrient storage

autophagy

insulinreceptor

PIP2 PIP3 AKT

amino acids

IGF-BPIGF-BPDILP

TOR

Figure 6.8 Insulin/IGF signaling (IIS) and the Target of Rapamycin (TOR) signaling in the fat cell serves as a nutrient-sensing

system to maintain energy homeostasis. The release of Drosophila insulin-like polypeptide (DILP) from the insulin-like

growth factor binding proteins (IGF-BPs) allows the DILPs to be accessible to the Insulin receptor and activates the IIS

pathway. The IIS pathway promotes growth through the control of protein synthesis and autophagy via TOR, contributes to

energy homeostasis by regulating carbohydrate storage and enhances translation by repressing FOXO. TOR signaling can

also be activated by free amino acids present in the cell. FOXO can act as a translational repressor.



are more resistant to starvation than three-day-old

feeding adults (Fig. 6.9a). These immature adults

have nearly 100% of their larval fat cells, while

in the three-day-old feeding adults the larval fat

cells have undergone cell death and are absent

(Fig. 6.9b). In transgenic flies, where programmed

cell death is delayed, starvation resistance of the

immature adult is further increased from 58 hours

to 72 hours (Fig. 6.9c). Although this appears to

be counter-intuitive, cell death is a mechanism for

the rapid release of energy stores from fat cells

into the hemolymph for uptake in other tissues

(including ovaries to support the final steps in

tissue maturation). Preservation of the fat cells

maintains the energy reservoir for a measured

mobilization in response to starvation. Thus, the

larval fat cells serve as a nutrient reservoir that can

be mobilized in response to stress to support the

survival of the adult.

6.3 Function as an endocrine organand nutritional sensor

The insect fat body has emerged as a dynamic

tissue that functions as an endocrine organ to

ensure proper energy homeostasis and as a sensor

to integrate larval nutritional status with maturation

signals for metamorphosis. The fat body coordinates

the growth of multiple tissues with the energy

demands of the organism and is involved in

determining body size. For example, a reduction in

the ability of the fat body to sense amino acids leads

to a reduction in both cell growth and cell

proliferation of other tissues, such as the larval

salivary glands and imaginal discs.

6.3.1 The fat body as an endocrine organ

In holometabolous insects the larval stage is

characterized by rapid growth of larval tissues

(e.g., fat body, salivary glands, Malpighian tubules,

trachea, muscle and epidermis) by increasing cell

time (h)

0 12 24 36 48 60

10-day-oldadults

3-day-oldadults

surv

ival

(%

)

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100(b)

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Lsp2::GFPLsp2::GFP/UAS-p35Lsp2::GFP/UAS-diap 1UAS-diap1/+;Lsp2::GFP/+

24 36 48time (h)

60 72 84 96

Figure 6.9 The role of larval fat cells in adult Drosophila

melanogaster. (a) Survival of starved adults of different

ages. (b) Number of larval fat cells in fed adults, and

survival of starved adults over six days after eclosion.

(c) Effect of retention of larval fat cells on survival of

starved flies. Three genetic routes to prevent programmed

cell death of larval fat cells were applied (diamond, circle,

triangle), with wild-type controls (square). The LD50 for

control flies was <60 hours and for genetically

manipulated flies was 84 hours (reproduced from Aguila

et al. 2007).

142 Fat body


size via endomitosis, and the cellular proliferation

of the precursors to the adult tissues (imaginal discs)

using the mitotic cell cycle. The insect fat body

has a central role in fueling this growth through

its participation in intermediary metabolism (i.e.,

generation of ATP) and in coordinating growth

with nutritional status through the production of

growth factors.

Since the initial efforts to culture insect cells

and tissues, the addition of fat body or fat-body

conditioned medium was found to be an important

requirement for in vitro cell proliferation and

differentiation. For example, the maintenance

of D. melanogaster imaginal discs in culture

required fat-body conditioned medium in addition

to insulin and a juvenile hormone analog. These

supplements are also needed for optimal growth

and normal cell division in cultured lepidopteran

imaginal discs and Manduca sexta midgut

stem cells.

The fat body of D. melanogaster produces at

least two classes of growth factors: the imaginal

disc growth factor family (IDGFs), and the adenosine

deaminase-related growth factors (ADGFs). The

ADGFs stimulate imaginal disc proliferation, and

one of them, ADGF-D, is produced primarily by the

fat body and brain. The IDGF family is produced by

embryonic yolk cells and the fat body of the embryo

and larva and might correspond to the mitogenic

factors responsible for growth in fat-body

conditioned media. IDGF1 and IDGF2 promote

imaginal disc cell proliferation in vitro and are

likely to act through the Drosophila insulin receptor

to promote cell growth. It appears that control of

larval cell growth, as well as the imaginal cell

proliferation, is regulated by fat body mitogenic

growth factors.

In addition to the secretion of growth factors,

the fat body is a key player in the synthesis of the

insect molting hormone, 20-hydroxyecdysone (20E).

Although the precursors of 20E are synthesized in the

prothoracic gland (Section 15.4.2), the final step in

20E synthesis occurs in the peripheral tissues, e.g.,

the fat body. Specifically, P450 monooxygenase

CYP314A1 (Shade protein in D. melanogaster)

hydroxylates alpha-ecdysone to form the active

form of the hormone, 20E. Orthologs of the CYP314A1

gene have been found in Hymenoptera, Coleoptera,

Lepidoptera and Diptera, but functional studies

of these monooxygenases have only been carried

out in dipterans and lepidopterans. Studies in

D. melanogaster have shown that conversion of

alpha-ecdysone to 20E during the larval and pupal

stages occurs predominantly in the fat body, with

other organs such as the Malpighian tubules and

midgut contributing small amounts of monoxygenase

activity.

6.3.2 Monitoring nutritional status

Two major signaling pathways, the insulin/IGF

signaling (IIS) and the Target of Rapamycin

(TOR) pathway are active in the fat body of

D. melanogaster and are involved in maintaining

a stable equilibrium between energy storage and

utilization (Fig. 6.8). In insects, the IIS and TOR

signaling pathways are integrated to regulate

growth, nutrient storage and autophagy, a catabolic

process used to degrade the cell’s own components

through the lysosomal machinery. Autophagy is a

major mechanism by which a starving cell

reallocates nutrients from unnecessary processes to

more-essential processes. In addition to activation

by IIS, the TOR signaling pathway can be activated

by amino acids.

Several putative amino acid transporters

have been identified in the fat body. One of these,

Minidisks, is predominately expressed in the fat body

and is necessary for imaginal disc proliferation in

D. melanogaster. Another amino acid transporter,

Slimfast, is required for proper growth of the

endoreplicating cells, which make up most of the

larval tissues. Fat body lacking Slimfast also have

down-regulated TOR activity, thus connecting this

amino acid transporter to the nutrient-sensing

mechanism in the fat body.

6.3 Function as an endocrine organ and nutritional sensor 143


Summary

� The fat body is in the hemocoel, and the proximity of the cells to the hemolymph

facilitates the exchange of metabolites. The dominant cell type of the fat body is

the trophocyte, but the fat body of some insects additionally have urate cells,

mycetocytes or oenocytes.

� The fat body is of mesodermal origin. In hemimetabolous insects the fat body

persists into adulthood. In holometabolous insects the fat body cells disaggregate at

metamorphosis, and either the organ reforms from these cells in the adult, or the

larval fat body cells are eliminated with the adult fat body cells generated de novo.

� The fat body is rich in lipids, especially triacylglycerols, and glycogen. It is also

responsible for the synthesis of many hemolymph proteins and major storage

proteins, including vitellogenin and arylphorins.

� Fat body cells have active insulin-like peptide and TOR signaling, which play central

roles in mediating the regulated growth and nutrition of the insect.

Recommended reading

Arrese, E. L. and Soulages, J. L. (2010). Insect fat body: energy, metabolism, and

regulation. Annual Review of Entomology 55, 207–225.

Boggs, C. L. (2009). Understanding insect life histories and senescence through a resource

allocation lens. Functional Ecology 23, 27–37.

Hoshizaki, D. K. (2005). Fat-cell development. In Comprehensive Molecular Insect Science,

ed. L. I. Gilbert, K. Iatrou and S. Gill, pp. 315–345. Oxford: Elsevier

Mirth, C. and Riddiford, L. (2007). Size assessment and growth control: how adult size is

determined in insects. Bioessays 29, 344–355.

References

Aguila, J. R., Suszko, J., Gibbs, A. G. and Hoshizaki, D. K. (2007). The role of larval fat cells

in adult Drosophila melanogaster. Journal of Experimental Biology 210, 956–963.

Butterworth, F.M., Bodenstein, D. and King, R. C. (1965). Adipose tissue of Drosophila

melanogaster I: an experimental study of larval fat body. Journal of Experimental

Zoology 158, 141–154.

144 Fat body


Dean, R. L., Locke, M. and Collins, J. V. (1985). Structure of the fat body. In Comprehensive

Insect Physiology, Biochemistry and Pharmacology, vol. 3, ed. G. A. Kerkut and L. I.

Gilbert, pp. 155–210. Oxford: Pergamon Press.

Gies, A., Fromm, T. and Ziegler, R. (1988). Energy metabolism in starving larvae of

Manduca sexta. Comparative Biochemistry and Physiology 91A, 549–555.

Haunerland, N. H., Nair, K. N. and Bowers, W. S. (1990). Fat body heterogeneity during

development of Heliothis zea. Insect Biochemistry 20, 829–837.

Hoshizaki, D. K. (2005). Fat-cell development. In Comprehensive Molecular Insect Science,

ed. L. I. Gilbert, K. Iatrou and S. Gill, pp. 315–345. Oxford: Elsevier.

Locke, M. (1970). The molt/intermolt cycle in the epidermis and other tissues of an insect

Calpodes ethlius (Lepidoptera, Hesperiidae). Tissue & Cell 2, 197–223.

McDermid, H. and Locke, M. (1983). Tyrosine storage vacuoles in insect fat body. Tissue &

Cell 15, 137–158.

Summary 145

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